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D J Ruiter

Publications and source records attributed to D J Ruiter.

At least 73 records · Page 4Linked to original sources
PubMed1998

An atypical form of bullous congenital ichthyosiform erythroderma is caused by a mutation in the L12 linker region of keratin 1.

Defective keratins are the cause of a number of hereditary disorders of the epidermis and other epithelia. The disease-causing mutations in keratins are clustered in the rod domain, and mutations in the helix boundary peptides cause the most severe forms of epidermal fragility syndromes. Siemens described a family with an atypical, mild form of bullous congenital ichthyosiform erythroderma. Linkage analysis in this family indicated that a defective type II keratin might be the underlying cause, keratins K1 and K2e being the best candidates. A substitution of valine for aspartic acid was detected at position 340 (D340V) in the L12 region of the K1 polypeptide. The mutation was found to cosegregate with the disorder in the family. Herewith, a genotype-phenotype correlation is shown for bullous congenital ichthyosiform erythroderma comparable with that described for epidermolysis bullosa simplex.

Genetic Linkage↗
PubMed1998

Epitopes of components of the plasminogen activation system are re-exposed in formalin-fixed paraffin sections by different retrieval techniques.

We present a systematic analysis of the sensitivity and specificity of immunohistochemical stainings for components of the plasminogen activation system, i.e., uPA, tPA, PAI-1, PAI-2, and uPAR, on routinely processed (formalin-fixed, paraffin-embedded) tissues. Five to nine antibodies per component were tested and the influence of different antigen retrieval regimens on immunoreactivity was investigated. We studied six different microwave-mediated pretreatments and two pretreatments by proteolytic digestion. First, positive and negative control tissues were stained. Then, frozen and paraffin sections from the same cancer lesions were stained after specific modes of pretreatment and with selected antibodies. For each component, one or a few of the tested Abs gave optimal staining on paraffin sections when combined with a particular tissue pretreatment. For PAI-1, and to a lesser degree also for tPA, an underrepresentation of stromal cell staining in paraffin material was found, whereas tumor cells showed good staining. For uPA, PAI-2, and uPAR, consistent staining results were obtained on paraffin sections.

Animals↗
PubMed1998

Proteases in cutaneous melanoma.

From a great number of studies there is clear evidence that several extracellular proteolytic enzymes play an important role in various tumour-related processes. This review focusses on proteases in cutaneous melanoma. The current knowledge on and insights into the involvement of proteases in tumour progression are based on in vitro studies, on animal model studies and on investigations using patient material. In the field of melanoma, these three modalities are also applied to the investigation on the impact of proteases. Consequently, the current review summarizes research on both human melanoma cell lines and human melanocytic lesions. In addition, results obtained from animal experiments are included.

Animals↗
PubMed1998

Endothelial P-selectin expression is reduced in advanced primary melanoma and melanoma metastasis.

Some malignant tumors induce a cellular immune response that results in the formation of an inflammatory infiltrate and subsequent tumor regression. The infiltrating leukocytes extravasate from the bloodstream after binding to adhesion receptors on the surface of the endothelium. One of these receptors is the P-selectin molecule (CD62P) that is constitutively present on normal capillaries. We observed that P-selectin expression is absent from the microvasculature in advanced primary melanoma and in melanoma metastasis in contrast to benign melanocytic lesions where P-selectin expression was identical to that in normal skin. We suggest that one of the mechanisms by which advanced melanoma lesions evade inflammatory regression operates via a decrease of endothelial P-selectin expression.

Antigens, Surface↗
PubMed1998

Identification of multiple mRNA and DNA sequences from small tissue samples isolated by laser-assisted microdissection.

Molecular analysis of small tissue samples has become increasingly important in biomedical studies. Using a laser dissection microscope and modified nucleic acid isolation protocols, we demonstrate that multiple mRNA as well as DNA sequences can be identified from a single-cell sample. In addition, we show that the specificity of procurement of tissue samples is not compromised by smear contamination resulting from scraping of the microtome knife during sectioning of lesions. The procedures described herein thus allow for efficient RT-PCR or PCR analysis of multiple nucleic acid sequences from small tissue samples obtained by laser-assisted microdissection.

Base Sequence↗
PubMed1997

[Dysplastic nevi and the risk of melanoma: a guideline for patient care. Nederlandse Melanoom Werkgroep van de Vereniging voor Integrale Kankercentra].

Consensus was recently reached in the Netherlands regarding the clinical management of dysplastic naevi and the definitions in clinical and pathological diagnostics. The term 'dysplastic' is reserved for histological diagnostics; the term preferred for clinical use is 'clinically atypical naevus'. A naevus is defined as clinically atypical if it meets three of the following five criteria: > or = 5 mm in diameter, vaguely bordered, asymmetrically shaped, irregularly pigmented and a red hue (erythema). Presence of clinically atypical naevi is a main risk factor for melanoma. Dysplastic naevus syndrome (DNS) is present if a patient has a melanoma and one or several clinically atypical naevi. The diagnosis of 'familial DNS' (familial atypical multiple mole-melanoma syndrome, abbreviation FAMMM syndrome) is made if at least two close relatives (including the patient) are known with a melanoma with or without atypical naevi, while one or several (other) relatives have atypical naevi. The risk of melanoma in a gene carrier of familial DNS is close to 100%, while multiple melanomas develop in 30% of the gene carriers. No DNA diagnostics is yet possible in most DNS/FAMMM families, because of the involvement of genes yet unknown. Accordingly, at present it is still too early for DNA diagnostics. Currently, therefore, the diagnosis is based only on anamnestic, clinical and histological grounds.

Clinical Protocols↗
PubMed1997

[2nd revised consensus skin melanoma. De Nederlandse Melanoom Werkgroep].

The 'Guideline melanoma of the skin, second revised consensus' was published in March 1997. Some of the contents are cited: Over 1600 new melanomas are diagnosed in the Netherlands each year; by now the mean 5-year survival amounts to over 80%. In examination of a pigmented lesion a dermatoscope is a valuable tool. The recommended margin of the diagnostic excision was reduced from 5 mm to 2 mm of macroscopically normal skin round the lesion; the margins in definite excision are: 1 cm of normal skin for a Breslow thickness < or = 2 mm; 2 cm for a Breslow thickness > 2 and < or = 4 mm. A margin of at least 2 cm seems also justified for thicker melanomas. Elective (prophylactic) regional lymph node dissection is advised against. Sentinel node biopsy appears to be an attractive method to detect occult metastasis in regional nodes. In lymph node metastasis a (therapeutic) regional lymph node dissection should be performed. In case of inoperable tumourgrowth in an extremity regional isolated perfusion is indicated. Radiotherapy may be applied curatively (e.g. if surgery is not possible), palliatively (if desired in combination with hyperthermia) or postoperatively (if non-radical resection is suspected). Adjuvant systemic therapy in melanoma patients is still experimental; the earliest results of high doses of interferon alpha are encouraging. Atypical (dysplastic) naevi and congenital naevi are important risk factors for melanoma. No consensus was reached regarding prophylactic removal of all congenital naevi. Regarding the duration of the follow-up period, 5 years suffices in patients with a melanoma with a Breslow thickness < or = 1.5 mm (provided there are no histological signs of regression), while 10 years is required for melanomas with a Breslow thickness > 1.5 mm. The patient should be actively involved in the follow-up (inspection, palpation). Routine blood testing, roentgen examination or ultrasonography are considered to be useless. There are no indications that hormonal alterations during pregnancy or use of the pill stimulate the growth of micrometastases that may be present. Excessive exposure to ultraviolet rays is discouraged.

Biopsy↗
PubMed1997

Heterogeneous expression of immunotherapy candidate proteins gp100, MART-1, and tyrosinase in human melanoma cell lines and in human melanocytic lesions.

In recent years, it has become evident that T cells can recognize peptides of melanocytic lineage antigens such as gp100, MART-1, and tyrosinase at the tumor cell surface and can subsequently destroy these cells. It is thus feasible to develop immunotherapeutic approaches based on the melanocytic marker profiles of melanoma cells. One of the predictors of the success rate of such a treatment is the extent of positive (target) tumor cells within the lesions of the patient. First, we investigated the presence of these three proteins in 18 human melanoma cell lines using RT-PCR and immunohistochemistry. In 11 cell lines, mRNA and protein of all three markers could be detected; in one cell line, only two markers were present, and six melanoma cell lines showed no evidence for these markers. Secondly, we stained frozen sections of 105 human melanocytic lesions, 13 common nevocellular nevi, 13 atypical nevi, 13 early primary melanomas (Breslow < 1.5 mm), 25 advanced primary melanomas (aPM; Breslow > or =1.5 mm), and 41 melanoma metastases (MM) with antibodies against glycoprotein 100, melanoma antigen recognized by T cells, and tyrosinase. In addition, we used the 3,4-dihydroxy-L-phenylalanine reaction to detect tyrosinase enzyme activity as a confirmation of the tyrosinase immunohistochemical results in a subset of the lesions. In the benign lesions, glycoprotein 100 was more prominently expressed in epidermal melanocytes, whereas melanoma antigen recognized by T cells was encountered in all or nearly all dermal melanocytes in all nevocellular nevi and atypical nevus lesions. Tyrosinase was found in a lower percentage of melanocytes, both in the epidermis and in the dermis within these lesions. With regard to heterogeneity of staining within the malignant lesions, we found that 54% (early primary melanomas), 48% (aPMs), and 56% (MM) of the lesions stained within the same staining category for all three proteins studied. Approximately 17% of the aPM and MM lesions did not show positive tumor cells for any of the three proteins. We conclude that a subgroup of patients with high expression should be selected for immunotherapeutic treatment approaches based on the presence of these proteins.

Antigens, Neoplasm↗
PubMed1997

Immunohistochemical analysis of integrin alpha vbeta3 expression on tumor-associated vessels of human carcinomas.

Expression of the alpha vbeta3 integrin is upregulated on sprouting endothelia. Systemic application of antibody or peptidic inhibitors of alpha vbeta3 function disrupts tumor angiogenesis and reduces growth and invasiveness of human tumors in animal models. We systematically investigated alpha vbeta3 expression on tumor-associated vessels of 4 different human epithelial tumors and the corresponding normal tissues by means of immunohistochemistry on frozen sections using the alpha vbeta3-complex specific monoclonal antibody LM609. Variable levels of LM609 staining were found in all carcinoma lesions. A considerable number of tumor tissues (35/50) expressed alpha vbeta3 on more than 50% of their vessels. Inflammatory infiltrates and the possibly hypoxic conditions near necrotic areas of tumors were accompanied by an increased alpha vbeta3 expression. Remarkably, the vasculature in apparently normal tissue also stained for alpha vbeta3. However, the percentages of stained vessels and their staining intensity were lower than in neoplastic tissues. Besides the vascular alpha vbeta3 expression, several extravascular cell types stained positive, in both normal and tumor specimens. Taken together, our findings show a considerable number of colon, pancreas, lung and breast carcinoma lesions with many alpha vbeta3-expressing vessels that could be targets for anti-alpha vbeta3-therapy.

Adenocarcinoma↗
PubMed1997

Quality assessment by expert opinion in melanoma pathology: experience of the pathology panel of the Dutch Melanoma Working Party.

Some cutaneous melanocytic lesions are notoriously difficult to diagnose by histopathology. For that reason, the Pathology Panel of the Dutch Melanoma Working Party was instituted and is regularly approached to provide an expert opinion on problem cases. In order to identify the most common diagnostic problems, 1069 consecutive referral cases of submitted lesions (1992 to 1994 inclusive) were analysed. About 60 per cent of the requests came from small laboratories, with up to three consultant pathologists. Two-thirds of the lesions reviewed concerned women and nearly 50 per cent of the patients were 30 years of age or younger. In 8 per cent of the cases, the referring pathologists felt unable to make a confident diagnosis; in 14 per cent, melanoma was suspected; and in 12 per cent, a differential diagnosis only had been formulated. The panel felt able to provide an unequivocal diagnosis in 93 per cent of the requests. Of the 158 lesions classified as 'invasive melanoma' by the referring pathologists, 22 were considered to be benign by the panel. Conversely, 108 invasive melanomas (panel diagnosis) had originally been considered as benign lesions, dysplastic naevi or melanoma in situ. These high numbers of discordancies reflect the intrinsic difficulty of the differential diagnoses in this selected material submitted to the panel. Diagnostic difficulties were most often encountered with Spitz naevi and dysplastic naevi. Although the rate of overdiagnosis and underdiagnosis is quite high, in the majority of cases the diagnosis of the referring pathologist matched the diagnosis of the panel. This may reflect a proper awareness of difficult melanocytic lesions in pathology practice. The activities of the Pathology Panel of the Dutch Melanoma Working Party contribute to the improvement of the quality of diagnosis in cutaneous melanocytic lesions, as they increase the number of unequivocal diagnoses and reduce the number of incorrect diagnoses. On the basis of the systematic comparison of the diagnosis by the referring pathologist and the panel, postgraduate teaching and quality control can be more focused on specific diagnostic problems.

Adolescent↗
PubMed1997

Cytokeratin and vimentin expression in normal epithelium and squamous cell carcinomas of the larynx.

The immunohistochemical expression patterns of cytokeratin polypeptides and vimentin were investigated in normal epithelia and squamous cell carcinomas of the larynx with special emphasis on tumor grading. During malignant transformation of epithelial cells, the cytokeratin expression patterns changed, depending on the differentiation grade of the carcinomas. In low-grade carcinomas, the expression patterns were close to those of the normal epithelium. With increasing tumor grade, there was decreased expression of stratification cytokeratins and increased expression of basal cell, simple cell and hyperproliferation-related cytokeratins. Increasing tumor grade was also associated with the expression of vimentin, a cytoskeletal protein of mesenchymal cells. No relationship was found between vimentin expression and the presence of lymph-node metastases.

Biomarkers, Tumor↗
PubMed1997

Angiogenesis in brain tumors; pathobiological and clinical aspects.

Angiogenesis is the outgrowth of new blood vessels from the preexistent vasculature. In 1971, Folkman hypothesized that solid tumors are dependent on angiogenesis for sustained growth and that anti-angiogenic treatment is a potential antineoplastic therapy. Because glioblastoma multiforma (GBM) frequently shows florid microvascular proliferation (MVP), this tumor has been considered since then as a suitable candidate for such treatment that attempts to eradicate or control a neoplasm by interfering with its blood supply. Indeed, in animal models the growth of glioma xenografts can be inhibited by targeting the angiogenic process. However, unlike many glioma xenografts, human infiltrating gliomas such as GBMs have a diffuse infiltrative growth pattern, and preexistent vessels may suffice to provide many tumor cells with much of their blood supply, particularly in the critical peripheral infiltrative margins. Thus, while attractive in concept, anti-angiogenic therapy of GBM must address the anatomic vascular realities of this neoplasm. Even if anti-angiogenic therapy ultimately has a role in infiltrative neoplasms, there are a host of other intracranial neoplasms whose discrete architecture might make them attractive candidates for anti-angiogenic therapy. This review summarizes the angiogenic process in GBM and suggests other types of tumors for which the efficacy of anti-angiogenic therapy might be studied.

Brain Neoplasms↗
PubMed1997

Vascular density in melanoma xenografts correlates with vascular permeability factor expression but not with metastatic potential.

We studied the relation between tumour vascular density and tumour growth rate, metastatic incidence and vascular permeability factor (VPF) mRNA levels in a human xenograft model described previously. Vascular density was determined by automated image analysis. Xenografts derived from cell lines BLM and MV3 showed the highest mean vascular density (MVD), the highest in vivo growth rate, high VPF mRNA levels and rapid development of lung metastases. Xenografts of cell lines M14, Mel57 and MV1 showed a significantly lower degree of vascularization, lower in vivo growth rates and lower levels of VPF mRNA, but formed lung metastases with a similar incidence as those of BLM and MV3. Xenografts from cell line 1F6 did not form lung metastases, whereas tumours derived from a spontaneous mutant of 1F6, designated 1F6m, gave rise to lung metastases to the same extent as Mel57, M14 and MV1 tumours. MVD values in 1F6 and 1F6m xenografts, VPF mRNA levels and in vivo growth rates of 1F6 and 1 F6m xenografts, however, were similar. In conclusion, in the melanoma xenograft model vascular density is correlated with in vivo growth rate and with in vitro VPF mRNA levels, but not with the ability to metastasize.

Animals↗
PubMed1997

The role of amyloid in the pathogenesis of Alzheimer's disease.

Since the identification in 1984 of the amyloid beta protein (Abeta) as the major component of senile plaques and cerebrovascular amyloid in Alzheimer's disease (AD) brains, it is well accepted that the production of this protein is a crucial factor in the pathogenesis of AD. Abeta is produced by cleavage from the amyloid precursor protein (APP) and can form fibrils in vivo and in vitro. The formation of these fibrils is influenced by proteins that are found in association with Abeta-containing lesions in the AD brain. Several of these proteins arise by an inflammatory response of the brain to Abeta production. The distribution of different isoforms of Abeta, varying at the C-terminus of the peptide, varies among the Abeta-containing lesions in AD brains. Such variations may have consequences for the pathogenesis of AD because the various Abeta isoforms differ in their capacity to form fibrils, and they have different toxic effects on neurons and vascular cells, respectively. The experimental data indicate that the pathogenesis of senile plaques is different from the generation of cerebrovascular amyloidosis. Summarizing models for either type of AD pathology are presented.

Alzheimer Disease↗
PubMed1997

Lack of lymphangiogenesis in human primary cutaneous melanoma. Consequences for the mechanism of lymphatic dissemination.

Cutaneous melanoma has an initial preference for lymphatic spread. Remarkably, melanoma progression toward this metastasizing phenotype is accompanied by intense blood vessel angiogenesis (hemangiogenesis), but lymphangiogenesis, the formation of new lymph vessels in the tumor, has never been reported. To investigate how primary melanoma cells interact with the existing lymphatic microvasculature, and whether lymphangiogenesis occurs, an immunostaining was developed that differentially decorates blood and lymph vessels in frozen tissue sections. The density and distribution of both these vessel types in and around thin (< or = 1.5 mm) and thick (> or = 1.5 mm) primary melanoma lesions and in normal and uninvolved skin were determined. Although especially in thick melanoma lesions a significant increase in blood vessel density was observed, lymphatic density remained unaltered, showing that lymphangiogenesis did not occur. Morphological analysis indicated, however, that melanoma progression is accompanied by a sequence of events that involves hemangiogenesis supporting tumor expansion, especially in the vertical growth phase. Often, stromal sepia are formed around the blood capillaries in the tumor neovasculature protecting them from invasion. Lymph vessels inside the tumor were infrequently observed. However, subepidermal lymph vessels often seemed to be entrapped and penetrated by the expanding tumor mass. In this way, hemangiogenesis, as the driving force behind tumor expansion, might indirectly increase the chance of lymphatic invasion in the absence of lymphangiogenesis. This model explains the paradox that, although melanoma metastasis seems to require angiogenesis, a consistent relation of prognosis with blood capillary density in primary cutaneous melanoma is lacking.

Biomarkers↗
PubMed1997

[Inflammatory mechanisms in the pathogenesis of Alzheimer's disease].

Senile plaques belong to the pathological hallmarks of the brains of patients with Alzheimer's disease. There is an increasing amount of evidence that the formation of senile plaques is accompanied by an acute phase reaction, involving the production of several inflammation-associated proteins and the activation of microglial cells. The products of these inflammatory reactions may contribute to the fibrillogenesis of the amyloid beta protein, the major constituent of senile plaques. Both fibrils of the amyloid beta protein and products of activated microglial cells may be neurotoxic, leading to neuronal degeneration and to clinical symptoms of dementia. Recent epidemiological findings have drawn attention to the possibility of therapy with anti-inflammatory agents. Although the results of these studies suggest a beneficial effect of such therapy, further study is warranted to gain more insight into the fundamental aspects of such treatment as well as to develop specific drugs that have little side-effects.

Acute-Phase Reaction↗
PubMed1997

Transition of horizontal to vertical growth phase melanoma is accompanied by induction of vascular endothelial growth factor expression and angiogenesis.

Melanoma progression in general is characterized by an increase in both metastatic frequency and the vascular density of the tumour tissue. Although a direct correlation between these two parameters in individual cases seems to be lacking, it is clear that metastasis is invariably preceded by angiogenesis. One of the angiogenic factors that is produced by human melanoma cells is vascular endothelial growth factor (VEGF). To investigate the role of this factor in the angiogenic process in primary cutaneous melanoma we determined the mean vascular density and the presence of VEGF protein in biopsies of human lesions. The results were compared with those found in normal skin or uninvolved skin from melanoma patients. In addition, we studied morphological and antigenic features of the proliferating neovasculature. We show that (1) the mean vascular density gradually rises along with melanoma progression, (2) transition of horizontal to vertical growth phase melanoma is accompanied by induction of VEGF protein expression and accumulation of this factor in the stroma, (3) vertical growth phase melanoma is often organized in nodules separated by septa containing blood vessels, but without lymphatics, and (4) blood vessel lumina in vertical growth phase melanoma are separated from tumour nodules by two basal lamina containing collagen type IV and the endothelium shows activated morphology and focal expression of the adhesion molecule E-selectin. Our findings indicate that VEGF is a prominent angiogenic factor in melanoma angiogenesis. Although its expression is induced during progression, the effect of VEGF on the incidence of metastasis is probably indirect.

Animals↗